Intestinal Fistula Surgery

The pathophysiology of all forms of small-bowel fistulas is related to the exposure of nonintestinal tissue to intestinal contents because of the fistula. The intestinal bacterial flora leads to contamination and eventual development of sepsis. The local effect of intestinal fluid can be damaging or corrosive to the nonintestinal tissue, leading to breakdown, erosions, and loss of normal organ or organ system function.

Small-bowel fistulas can be classified according to the anatomic structures involved, the etiology of the disease process leading to fistula formation, and the physiologic output (primarily for enterocutaneous fistulas),as follows:

• Anatomic classifications define the sites of fistula origin, drainage point, and whether the fistula is internal or external
• Physiologic classifications rely on fistula output in a 24-hour period
• Etiologic classifications (eg, malignancy, inflammatory bowel disease, or radiation) define the associated disease entity leading to the development of the fistula

Each type of classification system carries specific implications regarding the likelihood of spontaneous closure, prognosis, operative timing, and nonoperative care planning. These classification schemes are not exclusive; if possible, all three methods should be used to classify each fistula.

The etiology of small-bowel fistulas is important for determining the subsequent treatment. The common mechanisms of intestinal fistula formation are outlined below.

Trauma

Operative trauma is the most common cause of enterocutaneous fistula formation. Inadvertent enterotomies[4] and leakage from intestinal anastomoses result in leakage of intestinal contents with abscess formation. The abscess erodes through the abdominal wall, commonly at the surgical incision site or drainage site. This results in communication of the intestinal lumen with the skin surface, forming an enterocutaneous fistula (see the image below).

Intestinal anastomoses are susceptible to partial or complete dehiscence in the presence of impaired blood supply to the area, systemic hypotension, anastomotic suture line tension, perianastomotic infection, and diseased bowel segment anastomosis.

Exposure of the bowel to prosthetic mesh or a large abdominal defect can lead to wall erosion, resulting in enterocutaneous fistula. Intraperitoneal drainage tubes can erode into the intestinal lumen, leading to enterocutaneous fistula formation.

Penetration of the intestinal wall from a foreign body (eg, an ingested metallic object or a fish bone) can lead to enteroenteric fistula formation because of erosion into adjacent bowel loops. Fistulas do not commonly form in this way. Similarly, penetrating trauma (ie, stab wound) rarely results in enterocutaneous or enteroenteric fistula formation. Nephroenteric fistula formation because of penetrating flank trauma is slightly more common.

A secondary aortoenteric fistula may develop after aortic repair.[5]

Infection

Intestinal infections that erode through the wall cause an abscess and may lead to fistula formation between the intestine and an adjacent viscus, a solid organ, or the exterior of the body. Amebiasis, actinomycosis, tuberculosis, Salmonella infection, coccidiomycosis, and cryptosporidiosis can all result in periluminal abscesses and fistulas.

A solid-organ abscess, such as an amebic hepatic abscess, can erode into small-bowel loops. Similarly, rupture of a perinephric abscess can lead to nephroenteric fistula formation. Diverticular and appendiceal abscesses can also lead to enteroenteric or enterocutaneous fistula formation.

Appendicocutaneous fistulas are uncommon and occur most often after percutaneous drainage of an appendiceal abscess. In patients with Crohn enteritis, fistulas that occur in the right lower quadrant after an appendectomy usually arise because of the involved terminal ileum adhering to the healing abdominal incision. In these instances, the fistula rarely arises from the appendiceal stump.

Inflammation

Crohn disease leads to ulceration and chronic transmural inflammation of the intestinal wall. The serosa of a healthy viscus adheres to the diseased intestine. Adjacent bowel loops, bladder, colon, and vagina are commonly involved. Inflammation gradually progresses to microabscess formation and internal perforation in the ulcerated areas. The ulcerated areas penetrate through the bowel wall into the adjacent involved structure, leading to fistula formation. Enteroenteric, enterovesical, enterovaginal, and perineal fistulas develop frequently in patients with Crohn disease.[6]

Ulcerated bowel-wall perforation may also lead to interloop abscess formation. The abscess may erode into adjacent bowel loops, resulting in fistula formation.

Radiation injury and malignancy

Long-term radiation injury to the intestine leads to ischemic changes in the intestinal wall. Erosions and dense adhesions between bowel loops develop, which can result in enteroenteric fistula formation. Similarly, degeneration of malignant tumors of the intestine or solid abdominal structures can lead to erosion into adjacent bowel loops, leading to fistulas.

Congenital

Complete failure of the omphalomesenteric duct to obliterate results in an enterocutaneous fistula at the umbilicus (see the image below). This is a rare congenital form of enterocutaneous fistula. The appearance of feculent material at the umbilicus suggests the diagnosis, and surgical resection of the patent duct is performed.

Approximately 80-90% of all small-bowel fistulas occur because of operative intervention. Approximately 50% of small-bowel fistulas form because of inadvertent enterotomies in patients in which no intestinal anastomoses were performed; the remaining 50% are related to complete or partial disruption of intestinal anastomotic suture lines.

Approximately 10-20% of all small-bowel fistulas arise spontaneously in association with inflammatory processes, malignancy, radiation therapy, and infectious diseases. Of these 10-20%, Crohn disease accounts for 5-50%, cancer for 2-15%, peptic ulcer disease for 3-5%, pancreatitis for 3-10%, radiation therapy for 2-5%, and infections for 2-5%.

Surgical procedures that are commonly associated with postoperative fistula formation include reoperative procedures that require extensive lysis of adhesions, trauma surgery, mesh repair of ventral hernias, laparoscopic procedures, and surgery for cancer.

Crohn disease is the leading cause of spontaneous small-bowel fistulas, accounting for more than 50% of cases. Small-bowel fistulas develop in 20-40% of all patients with Crohn enteritis; half of these are enterocutaneous, and the remainder are internal fistulas to other abdominal viscera or organs.

Multiple factors predict spontaneous fistula closure and the mortality associated with intestinal fistulas. These factors guide the decision to institute conservative or surgical intervention. (See the image below.)

As late as the early 20th century, the mortality associated with enterocutaneous fistulas was quoted to be as high as 70-100%. This was attributable primarily to sepsis, severe electrolyte and fluid imbalances, and malnourishment. With the advent of parenteral nutritional support and aggressive treatment of sepsis, the mortality and morbidity associated with fistulas decreased to 30-50%. In the current treatment of intestinal fistulas, a multidisciplinary approach has helped decrease the mortality to 15-37%.

The wide range of the reported mortality represents the heterogeneous etiology and the varied patient population in which intestinal fistulas develop. Early morbidity and mortality occur as a consequence of severe electrolyte imbalances that may develop in high-output fistulas. The mortality has primarily been attributed to sepsis and multiple organ failure. This is more likely to develop in patients who are severely malnourished, have undergone radiation therapy, and have large abdominal defects and complex fistulas that are inadequately drained externally.

The spontaneous fistula closure rate has been reported to be in the range of 23-80%. This wide range reflects the multiple factors that affect fistula closure. The typical spontaneous closure rate is 30-35%, achieved through ensuring nutritional support and infection control. Ancillary surgical or interventional procedures in the form of drainage of abscess cavities are required in almost 20-30% of all fistulas that spontaneously close.

Of all fistulas that are likely to close spontaneously, 85-90% close within 4-6 weeks after the initiation of conservative management (ie, nutritional support, treatment of sepsis, control of fistula output). After 3 months of conservative treatment, fistulas that have not healed spontaneously will not heal.

Most fistulas should be treated conservatively for 4-6 weeks. Patients with fistulas that show signs of improvement during this period may continue to be treated conservatively with the expectation of closure. Conversely, patients who show no signs of improvement should undergo surgical treatment. In patients who undergo definitive surgical closure for treatment of fistulas, the fistula recurrence rate has been reported to be in the range of 13-34%.

In patients with intestinal fistulas, approximately 75-80% of all deaths can be directly attributed to sepsis and resultant multiple organ failure. The likelihood of spontaneous fistula closure in a patient with infectious complications is 16 times lower than that in a patient without associated infectious complications.

The rates of death and spontaneous fistula closure also correlate with fistula output. The chances of spontaneous closure are three times higher in patients with low-output fistulas than in those with high-output fistulas. Reports in the literature have suggested mortality figures of 32-54% for patients with high-output fistulas and 6-26% for those with low-output fistulas.

The organ of fistula origin is an important predictor of spontaneous closure but is not as directly related to mortality. Jejunoileal enterocutaneous fistulas and lateral duodenal fistulas are both high-output fistulas with an associated spontaneous closure rate of only 18-20%; both are more likely to require surgical intervention for closure.

The type of nutritional support (eg, parenteral vs enteral) also affects outcome. A higher mortality, mostly secondary to sepsis, is reported in patients who receive parenteral nutrition. The rate also reflects that patients with high-output fistulas requiring parenteral nutrition are the most critically ill. Enteral nutrition is more feasible in patients with low-output fistulas and is associated with a lower mortality.

Serum albumin level has been reported to be strongly predictive of both mortality and spontaneous fistula closure. One study found that an initial serum albumin level was less than 2.5 mg/dL in 55% of patients; of this 55%, those patients who had an associated complication carried a mortality of 64% and a spontaneous closure rate of 23%. Serum transferrin levels of greater than 200 mg/dL have also been associated with a higher rate of fistula closure and survival.

Patients who undergo postoperative fistula treatment at the same institution where the primary surgical procedure was performed are likely to have a spontaneous closure rate of 40%. In contrast, the spontaneous closure rate for a patient who is referred from an outside institution is only about 20%. Similarly, the mortality figures for patients from the same institution versus those referred from another institution are reported as 36% and 26%.

Advanced patient age does not independently correlate with spontaneous closure rates. Despite this, the observed spontaneous closure rate in elderly patients is lower because of a higher mortality from associated comorbid conditions and poor nutritional and physiologic reserves.

The clinical presentation of the various forms of intestinal fistulas depends on the organs involved. The predominant signs and symptoms are those of infection from intestinal bacterial contamination.

Enterocutaneous fistulas

Excessive drainage via the abdominal incision or via operatively placed drainage catheters is often the first indicator of a postoperative enterocutaneous fistula. The drainage typically consists of obvious intestinal contents or fluid with bile staining (see the image below).[7] The presence of purulent fluid may disguise the character of the intestinal fluids, leading to initial misdiagnosis of a wound infection. The presence of gas bubbles in the wound or drain output also indicates an intestinal connection.

If differentiation proves difficult, the patient may be given oral methylene blue, indigo carmine, or activated charcoal. The presence of these substances in the drainage confirms the presence of an intestinal leak.

The skin surrounding the area of the fistula is erythematous and indurated and may be fluctuant if an underlying collection is present.

Clinical signs of sepsis (eg, fever, tachycardia, chills) are common when the fistula is associated with undrained intraperitoneal abscesses and infection of the soft tissue of the abdominal wall.

Enteroenteric fistula

Radiologic studies are often used for initial diagnosis of enteroenteric fistulas. The studies are obtained to evaluate intestinal symptoms or abdominal pain. Diarrhea, abdominal pain, weight loss, and fever are common symptoms associated with enteroenteric fistulas of all etiologies.

Enteroenteric fistula symptoms are nonspecific and may be due to the underlying disease process (eg, Crohn enteritis, radiation enteritis) or the presence of the fistula. Abdominal tenderness may be present on physical examination. Occasionally, a palpable abdominal mass representing densely adherent bowel loops is present.

Enterovesical fistula

Urinary tract contamination with intestinal organisms leads to the development of urinary symptoms in more than 80-90% of patients with enterovesical fistulas. The common presenting urinary symptoms include bladder irritability, dysuria, pyuria, fecaluria, and pneumaturia. Fulminant urosepsis may develop, especially in patients who are immunocompromised from underlying disease or immunosuppressant medications. (See the image below.)

Nephroenteric fistulas

Typically, nephroenteric fistulas (see the image below) develop slowly because of chronic renal disease; thus, the most common initial symptom is chronic urinary tract infection (UTI). In contrast, nephroenteric fistulas that occur from penetrating trauma often present early with symptoms of UTI.

Patients may have flank pain, tenderness, and a mass. As the fistula becomes established, fecaluria, pneumaturia, fever, chills, and fulminant sepsis develop. A watery diarrhea can occur, and in the late stages, severe dehydration, uremia, and acidosis develop. Function of the affected kidney is rarely normal. Perinephric abscesses are common and may cause a mass effect, leading to further deterioration of function.

Enterovaginal fistulas

Purulent or feculent vaginal discharge is the most common presentation of enterovaginal fistula (see the image below). Sepsis from associated intraperitoneal abscesses is common, and these patients experience abdominal pain, fever, and chills. Patients may develop a UTI as a consequence of bacterial contamination ascending the urethra.

Aortoenteric fistula

Aortoenteric fistulas (see the image below) present with gastrointestinal (GI) bleeding because of a direct communication between enteric lumen (commonly duodenum) and arterial lumen. Initial herald or sentinel bleeding (eg, hematemesis, hematochezia, melena) is commonly mild and self-limited. Often, weeks to months later, the patient has an episode of massive GI hemorrhage.

Patients with a paraprosthetic-enteric fistula (see the image below) have a perigraft abscess or an aneurysm that communicates with the intestinal lumen. Sepsis and abdominal pain are observed on initial presentation. If the infection remains untreated, eventually a communication develops between the arterial and intestinal lumina, and GI hemorrhage occurs.

Subclinical ongoing bleeding leads to chronic anemia. A patient with an aortic prosthetic graft and evidence of either acute or chronic GI hemorrhage must be considered to have an aortoenteric fistula unless definitive proof to the contrary is available.

Although laboratory tests do not help diagnose or confirm the presence of intestinal fistulas, they are important for defining the patient’s clinical condition and guiding treatment.

A complete blood count (CBC) should be obtained. An elevated white blood cell (WBC) count suggests associated infection. Abscesses, soft-tissue infection adjacent to an enterocutaneous fistula, bacteremia, or bloodstream infection may be present. Elderly patients or those who are severely nutritionally depleted may not manifest an elevated WBC count as an indicator of infection.

An electrolyte panel is helpful. Electrolyte imbalances and dehydration are common in patients with high-output enterocutaneous fistulas because of intestinal fluid loss. Hypokalemia, hypochloremia, and metabolic alkalosis are observed in patients with high-output gastric fistulas. Patients with pancreatic and small-bowel fistulas have associated hyponatremia, hypokalemia, and metabolic acidosis. Nephroenteric fistulas are often associated with decreased renal function, which manifests as elevated creatinine and blood urea nitrogen (BUN) and a reduced glomerular filtration rate (GFR).

Serum albumin levels are used to predict fistula closure and mortality. In one study, a serum albumin level higher than 3.5 mg/dL was associated with no mortality, whereas a level below 2.5 mg/dL was associated with a mortality of 42%. Higher levels of short-turnover proteins (eg, serum transferrin, prealbumin, retinol-binding protein) are used to predict fistula closure. A serum transferrin level higher than 200 mg/dL is associated with a higher rate of fistula closure and a lower mortality and vice versa.

Patients who are bacteremic or septic have positive blood culture findings. Results of blood culture are used to direct antibiotic therapy to the appropriate organisms.

In a patient with an enterovesical fistula, urine analysis and culture are both are useful for initial confirmation of the diagnosis, as well as for directing antibiotic therapy to the appropriate organisms.

Computed tomography (CT) allows identification as well as guided drainage of associated abscesses or fluid collection. CT with oral contrast can also identify the site of the fistula.

Gastric, duodenal, and proximal small-bowel fistulas can be readily identified. The presence or absence of distal bowel obstruction can be revealed; if intraluminal contrast passes distal to the fistula site, then distal obstruction is unlikely. Passage of the oral contrast, as well as the early presence of contrast within the colonic lumen, can demonstrate the gastrocolic fistula tract. The presence of periaortic inflammation, air collection, or fluid collection characterizes aortoenteric fistulas.

Fistulography is performed to confirm and define the location of an enterocutaneous fistula. Closed-suction drainage catheters are placed under radiologic guidance to drain abscesses or fluid collections. If the drainage contents are clearly enteric, the area is allowed to drain adequately for 7-10 days. This period allows a tract to form.

The patient is stabilized with correction of electrolyte imbalances and administration of antibiotics. Water-soluble contrast is injected via the drainage catheter under fluoroscopy or during CT. Intraluminal passage of contrast confirms the presence and defines the origin of the fistula. A complete contrast study of the gastrointestinal (GI) tract should follow fistulography.

Small-bowel follow-through contrast radiography often identifies enteroenteric fistulas in patients with Crohn disease and chronic radiation enteritis. The study is obtained to evaluate nonspecific complaints of abdominal pain, cramping, diarrhea, and anorexia. All of these symptoms and signs are attributable both to the primary disease and to internal fistulas.

After oral administration of activated charcoal, the presence of charcoal granules in the discharge fluid also confirms the presence of an enterocutaneous fistula. The appearance of charcoal particles in urine or vaginal discharge after oral administration confirms an enterovesical fistula or an enterovaginal fistula, respectively.

After oral administration of methylene blue, emergence of the dye thorough an incision, a drain, or a skin defect confirms the presence of an enterocutaneous fistula. Similarly, this test has been used to confirm the presence of an enterovesical fistula or an enterovaginal fistula.

Although the use of methylene blue has been described in the surgical literature as a method for detecting intraoperative and postoperative anastomotic leaks, it has been curtailed because of reports of associated patient deaths. For this reason, methylene blue is not recommended as a means of detecting or confirming the presence of a fistula in situations where other investigative modalities can be used.

Diagnostic procedures may include the following:

• Upper GI endoscopy - The presence of bleeding and inflammatory thickening of the wall of the distal duodenum in a patient with an aortic prosthetic graft indicates an aortoenteric fistula
• Cystoscopy - Enterovesical fistulas are often identified on cystoscopic examination; the presence of an area of inflammation and active purulent or intestinal content drainage confirms the diagnosis

Indications for surgery for intestinal fistula depend on anatomic, physiologic, and etiologic classification. Once the fistula is appropriately classified, it is possible to predict the likelihood of fistula closure with nonsurgical treatment.

Intestinal fistulas are first treated medically. Many enterocutaneous fistulas close spontaneously if infection is controlled, nutrition is adequate, and distal obstruction is not present.[8]

Definitive operative correction remains the final step in the treatment of nonhealing small-bowel fistulas. Such procedures should be undertaken only after the patient has been stabilized and is in positive nitrogen balance, with normal protein indices. Usually, a minimum of 3-6 weeks is required. During this time, if the fistula appears unlikely to respond to conservative treatment, radiologic evaluation and surgical planning can be undertaken.

Indications for surgery for intestinal fistulas can be classified into those related to early surgical intervention and those related to delayed intervention. Deciding between early and delayed surgical intervention is complicated and depends on multiple prognostic factors.

Early surgery is infrequently required but may be necessary in the following circumstances:

• Sepsis or abscess formation not amenable to percutaneous drainage
• Complete distal intestinal obstruction
• Uncontrolled bleeding from fistula
• Removal of mesh or other foreign bodies
• Inability to control the fistula without surgical drainage
• Aortoenteric fistulas (definitively managed by means of emergency surgery as soon as the diagnosis is made)

Delayed surgery is most commonly indicated in patients whose fistulas have not healed after several (typically 4-8) weeks of comprehensive conservative treatment. Specific indications include the following:

• Continued high output from fistula after patient has been given nothing by mouth and started on parenteral nutrition
• Continued signs of infection after institution of adequate antibiotic therapy and drainage of associated abscesses
• Uncontrolled bleeding

In 1999, Campos et al used a combination of prognostic factors to develop a multivariate model that determined the probability of spontaneous closure and mortality associated with intestinal fistulas.[9] In their group of patients, spontaneous closure was most likely to occur in low-output postoperative fistulas, with no associated complications. The overall mortality was highest in patients with high-output fistulas and in those with associated infectious complication.

Despite this model, as well as previously defined prognostic factors, estimating the probability of spontaneous closure and mortality associated with a fistula remains difficult. Further applications of prognostic models to larger and diverse patient populations are necessary to validate these types of predictive models.

The use of minimally invasive techniques in the treatment of intestinal fistulas has been described. Laparoscopic resection of internal fistulas as well as enterocutaneous fistulas has been reported in the literature.[10, 11, 12, 13, 14] Fibrin glue applications, as well as porcine and bovine tissue plugs, have been successfully used to close enterocutaneous fistulas.[15] Further studies are required to define patient selection and outcomes in the use of these techniques to treat intestinal fistulas.

Initial treatment of intestinal fistulas is medical, including resuscitation, control of sepsis, local control of fistula output, nutritional support, pharmacologic management, and radiologic investigations. The final therapeutic step, if necessary, is definitive surgery to restore gastrointestinal (GI) tract continuity.[16] (See the image below.)

Enterocutaneous fistula

Most patients with GI fistulas experience significant fluid and electrolyte imbalances. Carefully monitored replacement of the losses is essential and is often paired with central venous monitoring to accurately estimate fluid deficits. Resuscitation aims to restore intravascular fluid volume and to ensure a urine output of 30 mL/hr or higher. The circulation volume deficits result from extracellular fluid losses, and replacement is best achieved with isotonic crystalloid solutions, such as normal saline or lactated Ringer solution.

Simultaneous electrolyte repletion is necessary. Isolated measures of serum levels may not reflect the degree of intracellular electrolyte depletion; thus, continued monitoring for ongoing losses is necessary. Patients with high output and proximal fistulas develop significant metabolic acidosis, which may necessitate intravenous (IV) administration of sodium bicarbonate.

Control of sepsis

Uncontrolled sepsis is a major cause of mortality in patients with small-bowel fistulas. Tachycardia, persistent fever, and leukocytosis indicate the presence of infection associated with the fistula. Patients are treated with broad-spectrum antibiotics and local drainage of abscesses (if present).

Most deep or intraperitoneal collections are amenable to drainage guided by computed tomography (CT) or ultrasonography (US). Of postoperative intra-abdominal abscesses, 15% are reported to be associated with fistulas. Percutaneous drainage allows temporary control of the fistula and may achieve long-term fistula healing in as many as 70% of patients whose abscesses are adequately drained.

Surgical drainage may be required if the abscess is not safely accessible. At the time of surgery, definitive repair of the fistula should not be attempted, because the presence of adjacent infection precludes healing. The abscess should be drained, and if necessary, the fistula should be completely exteriorized to the skin level to prevent further intraperitoneal fluid collection.

Local control of fistula

An attempt should be made to decrease fistula output by placing enteric drainage tubes proximal to the fistula (an important treatment step). Nasogastric or nasojejunal tubes are usually placed, and the patient is given nothing by mouth while total parenteral nutrition (TPN) is initiated. The goal of controlling enterocutaneous fistula output is to prevent the intraperitoneal accumulation of intestinal contents and to protect the skin from the effects of the intestinal contents.

Control of enterocutaneous fistula drainage is individualized according to the patient and the fistula output. Drainage with a simple catheter placed into the fistula tract invariably fails as a result of occlusion and inability to capture all of the output.

In some instances, low constant suction applied via a soft sump catheter into the fistula tract can contain fistula drainage. Adjacent or escaping fluid requires placement of a collecting bag, which can also be attached to low continuous suction. Various modifications of the use of drainage tubes within the fistula tract have been described. (See the image below.)

The skin surrounding the fistula opening is exposed to intestinal contents, and this leads to excoriation and breakdown. Skin protection is an important part of fistula output control and is achieved through the placement of a Hollister appliance, which consists of a karaya ring with adhesive backing to encircle the fistula opening. The ring is attached to an ileostomy bag that should be emptied frequently or continuously via an attachment to continuous suction.

Stomahesive is a skin barrier material that can be applied to eroded skin to protect and allow it to heal. It contains a mixture of pectin, gelatin, and carboxymethylcellulose in wafer form. The wafer is applied to the skin, and the ostomy appliance is applied over the wafer. Skin protectants (eg, zinc oxide cream, aluminum paste, karaya gum powder, tincture of benzoin) are used to liberally coat skin that is exposed to intestinal contents.

After the fistula output is locally controlled, the applied suction is gradually reduced and finally replaced with gravity drainage. Similarly, the caliber of catheter within the fistula opening is progressively decreased. This allows the fistula tract to slowly close and heal. This process requires the careful monitoring of fistula output as changes are made, as well as frequent evaluation of the skin surrounding the fistula.

Sponge vacuum dressings can be applied to low-output fistulas to keep the surrounding skin dry. Case studies have reported some success using vacuum dressings to heal fistulas. Larger studies are required to validate these findings and to identify the appropriate use of vacuum dressings in fistula treatment.

Nutritional support

Adequate nutritional support has a significant impact on the outcome of patients with GI fistulas.[17]

Total caloric requirements for a patient with an enteric fistula are calculated on the basis of the patient’s overall clinical condition and must take into account the degree of physiologic stress. Patients with localized infections and malnutrition require 30-40 kcal/kg/day, whereas patients with uncontrolled sepsis, shock, and multiple organ failure require 40-45 kcal/kg/day. The total caloric needs are met by glucose and fats; glucose provides approximately two thirds to three fourths of the total caloric requirements, and lipids provide the remainder.

Proteins are not taken into account in calculating the total caloric requirements. This allows for efficient protein sparing and for the occurrence of an anabolic state. Proteins are administered as amino acids in parenteral formulas and protein hydrosylates in enteral formulas. To ensure that enteric protein losses are adequately replaced, 1.5-2.5 g/kg/day of protein is required.

Fluid and electrolyte balances are maintained by frequent monitoring of serum electrolyte levels and by replacing losses. Similarly, vitamins and trace elements are added to enteral formulas and parenteral formulas to prevent deficiencies.

TPN provides initial nutritional support while control of infection and maturation of the fistula tract occur. Normal intestinal motility and function usually return once abdominal sepsis is controlled and fluid and electrolyte imbalances are corrected.

Enteral feeding may be initiated orally or via a catheter placed distal to the fistula. The feeds can be started in the form of an elemental diet while fistula output is monitored. If fistula output does not significantly increase, enteral nutrition is continued and TPN gradually decreased and then discontinued.

At one time, high-output fistulas were considered a relative contraindication for initiating enteral nutrition. However, studies have demonstrated that even these fistulas can be effectively treated with enteral nutrition. The benefits of enteral nutrition include decreased gut bacterial translocation and the tropic effects on the intestinal mucosa. Enteral nutrition also helps to avoid the complications associated with TPN. Of all patients with GI fistulas who are treated with TPN, 20-25% develop complications (usually catheter-related sepsis and subclavian vein thrombosis).

Patients with optimal intake levels of calories and protein have a mortality of 12% and a fistula closure rate of 73%. Patients who receive inadequate nutritional support have a mortality close to 55% and a fistula closure rate of only 19%.

Pharmacologic support

In addition to the treatment schemata outlined below, certain enteric fistulas require variations in the principles of medical treatment and timing of surgical intervention.

The use of histamine-receptor antagonists (eg, famotidine) can decrease proximal and gastric fistula secretions.

The somatostatin analogue octreotide can significantly decrease fistula output, though earlier fistula closure has not been consistently demonstrated.[18] A subcutaneous dose (100-250 μg) of octreotide is administered every 8 hours. Various studies have reported a demonstrable decrease in fistula output of as much as 50% within 24-48 hours of initiating treatment. This can reduce high-output fistulas to a manageable level, simplifying fluid and electrolyte treatment.

Routine use of somatostatin infusion and somatostatin analogues remains controversial. Although findings suggest reduced time to fistula closure, scant evidence exists of increased probability of spontaneous closure.

Patients with fistulas associated with Crohn disease benefit from anti-inflammatory agents. A short (7- to 10-day) course of cyclosporine has been shown to decrease fistula output, inflammation, and pain. The adverse effects of cyclosporine are hypertension, paresthesias, hirsutism, nephrotoxicity, and an increased incidence of sepsis. Closure of Crohn-associated fistulas has also been reported with the use of azathioprine and 6-mercaptopurine (6-MP). The adverse effects of these drugs include leukopenia, pancreatitis, paresthesias, nausea, and nephrotoxicity.

Infliximab is a chimeric monoclonal antibody to tumor necrosis factor alpha (TNF-α) that has been demonstrated to heal as many as 50% of chronic intestinal fistulas in patients with Crohn disease. Adverse effects, including headaches, abscess, upper respiratory tract infection, and fatigue, occur in more than 60% of patients. In a study of 48 patients with Crohn disease and enterocutaneous fistula, anti–TNF-α therapy resulted in complete fistula closure in 33% of the study group.[19]

The use of serial intrafistular injections of autologous bone marrow–derived mesenchymal stem cells for refractory Crohn fistulas has been described.[20]

Enteroenteric fistula

Patients with Crohn disease who develop enteroenteric fistulas are treated with bowel rest, long-term TPN, and pharmacologic therapy with 6-MP, cyclosporine, azathioprine, or infliximab. A large number of fistulas heal; patients with refractory disease or intolerance to medications undergo surgery.

Enteroenteric fistulas also occur in association with GI or intra-abdominal malignancies. For these patients, it is vital to exclude disseminated or unresectable disease before attempting resection for cure. Conservative treatment with bowel rest, TPN, and antibiotics is unlikely to be successful in achieving fistula cure. Patients who have an acceptable surgical risk benefit from resection and primary anastomosis of the fistular area.

Enterovesical fistula

Medical treatment consists of nutritional support and treatment of urinary tract infection (UTI) with broad-spectrum antibiotics. Definitive treatment is surgical resection of the fistula, involved intestine, and bladder wall.

Nephroenteric fistula

Correction of fluid and electrolyte imbalances and administration of broad-spectrum antibiotics are the first steps in the treatment of nephrogenic fistulas. Nutritional support via TPN is instituted. If urinary obstruction is present, a temporary nephrostomy tube or a retrograde ureteral catheter is placed. Associated abscesses or fluid collections are drained via percutaneously placed catheters.

Early surgical intervention is necessary, given that medical treatment alone rarely results in fistula healing. Traumatic nephroenteric fistulas are an exception to this rule; in the stable, infection-free patient, conservative treatment may resolve the fistula.

Enterovaginal fistula

Treatment entails control of sepsis, nutritional support, and local drainage via sump-drain placement. Whereas enterovaginal fistulas that occur as a result of infection may close without requiring surgical intervention, those associated with Crohn disease are unlikely to close spontaneously.

Aortoenteric fistula

Aggressive medical treatment with emergency planning for surgical intervention is necessary for aortoenteric fistulas. Treatment is initiated with IV administration of crystalloids, electrolyte repletion, and broad-spectrum antibiotics. Blood and blood products are administered as necessary. Central venous or Swan-Ganz catheter and intra-arterial lines are used for intravascular perioperative monitoring.

Definitive surgical treatment is undertaken on an emergency basis and involves resection of the infected aortic graft, extra-anatomic vascular bypasses, and resection and repair of the involved intestinal segment.

The surgical procedure for intestinal fistula treatment depends on the structures involved. The basic surgical principles for treatment of all intestinal fistulas include the following:

• The procedure involves resection of the intestinal segment, fistula tract, and the adjacent part of the involved structure
• In the absence of extensive infection or inflammation, primary anastomosis of the divided intestinal segments is done to reestablish GI continuity and repair of the involved structure to maintain function
• In the presence of extensive infection or inflammation, the divided intestinal segments are exteriorized and the surgical procedure modulated to allow replacement or maximal preservation of function
• A staged procedure is performed after the infection and inflammation subsides to reestablish GI continuity and carry out reconstruction of the affected structure

Enterocutaneous fistula

The surgical procedure is individualized on the basis of preoperative radiologic and intraoperative findings.

Resection of the involved intestinal segment with primary end-to-end anastomosis is the procedure of choice and allows successful healing in most patients.

Exteriorization of the proximal and distal ends of the intestine is performed in the presence of extensive intra-abdominal sepsis, for which primary anastomosis is not appropriate. An everted Brooke ostomy is created from the proximal end to allow for successful postoperative fitting of an appliance.

A bypass procedure (see the image below) is appropriate when dense adhesions are encountered within the pelvis that preclude extensive lysis of adhesions. The goal is to defunctionalize the intestinal segment containing the fistula. Ideally, intestinal continuity is also restored; the intestinal segment containing the fistula tract is removed later.

It is often hard to mobilize the distal intestinal segment adequately. In these instances, the proximal segment is mobilized and anastomosed to the transverse colon, while the distal segment is closed and left in place or exteriorized as a mucous fistula. If intestinal continuity cannot be restored, the ends are exteriorized, and a staged procedure is performed with an end-to-end anastomosis. Ideally—though this is not always possible—the staged procedure is completed when the fistula segment is removed later.

Direct suture closure of the fistula is rarely successful and is used only as a last resort in patients with dense abdominal adhesions that preclude enteroclysis or in debilitated patients who cannot tolerate prolonged anesthesia.

GI fistulas associated with large abdominal defects are challenging surgical problems and are associated with a high mortality. Multiple staged procedures are necessary, with the aim of reconstructing the abdominal wall while controlling the fistula. The fistula may be controlled with a Malecot or soft-sump catheter intubation, while the adjacent abdominal wall defect is covered with split-thickness skin grafts or musculocutaneous flaps.

Endoscopic clip application to treat enterocutaneous fistulas in patients with Crohn disease has been described and has shown some short-term effectiveness; further studies are needed.[21]

Enteroenteric fistula

The ideal procedure for surgical treatment of enteroenteric fistulas is en-bloc resection of the involved intestinal segment in continuity with the fistula tract. In the absence of associated infection or significant inflammation, a primary anastomosis of healthy bowel ends can be attempted. In the presence of associated inflammation or infection, a proximal diversion procedure with wide drainage of the abscess cavity is performed. This is followed in 4-6 weeks with a delayed resection of the involved intestine and fistula.

All attempts are made to conserve bowel length in both primary and staged procedures. Resection should be limited to the area of intestine involved in fistula formation. Extensive resection is not advantageous and only increases the risks of subsequent short-bowel syndrome and malabsorption. This is particularly true in patients with Crohn disease who may require additional intestinal resections.

Enterovesical fistula

Patients with enterovesical fistulas undergo surgical resection of the diseased intestine and the involved area of bladder wall. A primary anastomosis of the bowel is performed, and the bladder wall is closed in layers. The areas of repair are separated with interposition of omental tissue, if possible.

The presence of inflammation makes healing of an anastomosis or repair unlikely. The safer procedure in these instances is transection of the intestinal segment proximal and distal to the fistula, leaving the fistula tract in place. Both ends of the intestine are exteriorized. This allows the urinary tract to remain free of contamination from intestinal contents. The patient is treated with appropriate antibiotics. Once infection and inflammation resolve, a delayed surgical procedure can be performed to resect the fistula tract and intestinal segment with primary repair of the bladder wall.

Enterovesical fistula has been safely managed laparoscopically.[22] A study by Nevo et al found laparoscopic treatment of enterovesical fistula to be safe and effective in experienced hands.[13]

Nephroenteric fistula

Medical treatment alone is rarely successful in resolving nephroenteric fistulas. The surgical procedure of choice is either total or partial nephrectomy, with en-bloc resection of the fistula tract and the involved intestinal segment. The ends of the intestines are anastomosed primarily.

Partial nephrectomy is appropriate in patients whose renal function is not severely impaired (as is mostly observed in nephroenteric fistulas of traumatic origin). The presence of a contralateral functioning kidney is verified prior to a total nephrectomy.

In the presence of severe inflammation or infection, the intestine is not anastomosed primarily. The segments are exteriorized to skin level, and a delayed anastomosis is performed after inflammation and infection have subsided.

Enterovaginal fistula

Surgery is reserved for patients who do not respond to conservative treatment with antibiotics and drainage of associated abscesses. An en-bloc resection of the involved intestinal segment with fistula and affected vaginal wall is performed. The intestinal ends are anastomosed primarily; the vaginal defect may be closed primarily.

Resection of a cuff of vaginal tissue along with the fistula and involved intestine is the preferred surgical approach. A primary intestinal anastomosis should be performed if the surrounding inflammation permits. The vaginal defect may be left open to allow postoperative external drainage of the pelvis.

Enterouterine, enterocervical, and enterofallopian fistulas

Appropriate treatment of the underlying disease with a total hysterectomy is usually indicated. The resected intestinal ends are anastomosed primarily.

Aortoenteric fistula

Emergency surgical intervention is typically required for aortoenteric fistula. The aortic prosthetic graft is removed, and an extra-anatomic bypass procedure is performed. The intestinal defect is debrided and closed primarily. The presence of extensive inflammatory or devitalized tissue may necessitate intestinal resection and an end-to-end anastomosis.

Surgeons have reported successful resection of the aortoenteric fistula followed with in-situ replacement of the infected prosthesis with a new prosthetic graft or cryopreserved aortic homograft. This procedure is associated with the risk of recurrent fatal aortoenteric fistula.

Endovascular intervention may be an acceptable treatment alternative in appropriately selected patients.[23, 5]  Endoscopic application of hemostatic clips has been suggested as a potential therapeutic option, though only a few cases had been described as of mid-2021.[24]

In a study by Chopra et al, the presence of GI complications was associated with a tripling of the risk of mortality after aortoenteric fistula repair.[25]

Preparation for surgery

The duration of conservative treatment is individualized. If the patient attains good nutritional status, remains free of sepsis, and has fistula output that progressively decreases, conservative treatment may be continued. The spontaneous closure rate of intestinal fistulas is reported as 30-80%. More than 90% of all fistulas close spontaneously within 4-6 weeks; fewer than 10% close after 2 months, and none spontaneously close after 3 months. Failure of an enterocutaneous fistula to spontaneously close is associated with a number of factors. (See the image below.)

The acronym FRIENDS is commonly used to predict the likelihood of fistula closure. FRIENDS stands for the presence of Foreign body, Radiated bowel, Inflammation (commonly due to Crohn disease), Infection, Epithelialization of the fistula tract, Neoplasm, Distal intestinal obstruction, and pharmacologically administered Steroids. These indicate a low likelihood of fistula closure. Identification and possible correction of some or all of these factors increase the chances of fistula closure.

Delaying surgery permits peritoneal reaction and inflammation to subside, making a definitive surgical procedure easier and safer. Prior to surgical intervention for fistulas, control of infection and optimization of nutritional status are important. Surgical intervention is most commonly undertaken for persistent fistula drainage despite adequate conservative treatment.

The need for emergency or urgent surgical intervention for intestinal fistulas is uncommon. An undrained intraperitoneal abscess not amenable to drainage guided by computed tomography (CT) or ultrasonography (US) is most likely to necessitate emergency intervention. Other indications include the presence of complete distal intestinal obstruction, uncontrolled fistula bleeding, the presence of mesh or other foreign bodies, and an inability to control the fistula without surgical drainage.

Surgical planning for fistula repair is individualized according to the patient’s overall medical status, radiologic findings, and intraoperative findings. Prolonged surgery may be anticipated with significant fluid shifts. Appropriate preoperative planning includes the following:

• Ensure that the patient is euvolemic before the procedure
• Provide blood transfusions as required
• Administer appropriate antibiotics
• Place a central venous catheter to determine intravascular volume status and thereby to direct perioperative management
• Place a Foley catheter to monitor urine output

Operative details

The surgical approach to the peritoneal cavity is via an incision that is located away from the areas of potential infection, inflammation, and adhesions. If a previous midline incision is present, the abdomen can be entered in the midline above or below the incision. This minimizes the chances of encountering adhesions to the abdominal wall and inadvertent enterotomies. A transverse incision located away from previous incisions is also a good option and allows peritoneal entry in an area free of adhesions.

Adhesions are lysed by starting from the area with the least dense adhesions and progressively approaching the more dense areas of adhesions and inflammation. Extensive lysis of adhesions is performed to free up the bowel from the ligament of Treitz to the rectum. This allows a complete inspection to exclude the presence of interloop abscesses and areas of obstruction, which is especially important in patients who have complex fistulas as well as clinical and radiologic signs of obstruction.

Extensive adhesiolysis may not be safe or feasible in the presence of dense adhesions. In these instances, dissection is limited to the areas that correlate to the areas of fistula, abscesses, or obstruction as identified on preoperative radiologic examinations.

Certain maneuvers are helpful in facilitating lysis of adhesions. Sterile water-soaked or saline-soaked laparotomy pads are applied to the areas of adhesions. This creates local edema that allows easier dissection. Lysis is best performed by means of careful sharp dissection with a scalpel or Metzenbaum scissors. Blunt finger dissection had been associated with a higher incidence of enterotomies. The underlying bowel can be protected during the dissection by placing a hand behind the adhesions.

Resection with primary anastomosis of the section or sections of bowel containing the fistula is the optimal procedure. The fistula tract along with the adjacent wall of the structure involved is resected if possible.

The intestinal anastomosis is created by using healthy bowel ends and a two-layer closure. Exteriorization of the bowel ends to create controlled fistulas is an option if unresectable distal obstruction is present.

The defect in the structure involved is repaired primarily, if possible. An enterovesical fistula after resection leaves a bladder wall defect that is usually easily repaired in two layers. A vaginal defect following enterovaginal fistula resection may be left open to allow drainage and secondary healing or may be repaired primarily. After resection, aortoenteric fistulas mandate reestablishment of blood flow via the creation of extra-anatomic bypasses away from the area of infection.

Areas of complex fistulas involving multiple bowel segments where isolation is not feasible may benefit from a bypass procedure, which can allow fistula healing. Roux-en-Y bypass of the diseased area may be performed. A simple bypass of the fistula-containing segment via anastomosis of afferent and efferent limbs in continuity is ineffective (see the image below).

A densely adherent or unresectable fistula is bypassed by completely dividing the afferent and efferent limbs and reanastomosing the divided ends to reestablish intestinal continuity. Large defects of the bowel wall can be repaired with a serosal patch, typically using the proximal jejunum.

After completing the anastomosis, the remainder of the bowel is reexamined to ensure that no inadvertent enterotomies or serosal tears are present. Enterotomies are repaired by using a two-layer closure, with care taken to ensure that no narrowing of the bowel lumen occurs. Serosal tears may be repaired with Lembert sutures.

Prior to abdominal closure, available omentum is placed between the bowel and the abdominal wall or the areas of resected and repaired adjacent structures involved in the fistula formation.

Patients with large open abdominal walls or defects may be candidates for an abdominal closure using absorbable mesh. In a previously infected field, mesh carries the risk of recurrent infections and fistulas. Fascial closure through separating the components of the rectus abdominis muscle-fascia complex can be used to achieve abdominal closure.

Continued nutritional support is essential in the postoperative course. A feeding jejunostomy or gastrostomy tube may be placed if prolonged nutritional support is required.

The duration of GI decompression and the incidence of acalculous acute cholecystitis after definitive surgery for small intestinal fistula may be shortened by providing preoperative enteral nutrition via the nasogastric rather than the nasointestinal route.[26, 27]

In patients undergoing definitive surgical repair of enterocutaneous fistulas, use of an Enhanced Recovery After Surgery (ERAS) protocol may yield improved surgical outcomes (eg, reduced postoperative nausea and vomiting, a lower overall complication rate, and a shorter median hospital stay).[28]

Inadvertent enterotomies

Enterotomies commonly occur during lysis of dense adhesions, especially of bowel loops located within the pelvic cavity. The rate of inadvertent enterotomies during primary laparoscopic procedures has been reported as 1-4%, compared with less than 1% for procedures approached via primary laparotomy. For procedures that involve lysis of adhesions, laparoscopy has been associated with a 20-50% rate of inadvertent enterotomy, compared with a rate of 13-19% during repeat laparotomy for lysis of adhesions.

Careful sharp dissection under direct vision minimizes the occurrence of enterotomies. If recognized, they are immediately repaired with closure using a two-layer technique and without limiting the luminal diameter. Heineke-Mikulicz or Finney intestinal plasty procedures may be performed. If short-bowel syndrome (see below) is not a concern, segmental resection and anastomosis may be performed. After completion of the surgical procedure, the entire bowel length is examined for missed enterotomies.

Excessive blood loss

Dense and extensive adhesiolysis may result in significant blood loss in patients who, preoperatively, may be anemic and nutritionally depleted. All patients who undergo surgical intervention for enteric fistulas should have their blood typed and crossmatched prior to surgery. Blood and blood products are administered judiciously on the basis of operative losses and the patient's clinical condition.

Sepsis

Postoperative partial anastomotic breakdown or intraperitoneal contamination may lead to abscess formation. Manipulation of infected tissue during operative procedures may lead to bacteremia and sepsis.

Short-bowel syndrome

Short-bowel syndrome is likely to occur in patients who undergo resection of excessive lengths of small bowel. This may occur after a single surgical procedure or result from repeated resections for treatment of chronic intestinal pathology (eg, Crohn enteritis, complications from Crohn enteritis). Conserving a minimum of 45-60 in. (~115-150 cm) of healthy small bowel in the presence of a patent ileocecal valve precludes the development of short-bowel syndrome.

Recurrence of fistulas

After surgical repair of enterocutaneous fistulas, the risk of fistula recurrence has been reported to be in the range of 18-33%. The main predictive factor of recurrence is the surgical technique used: Wedge resection or oversewing of an enterocutaneous fistula carries a recurrence rate of 32.7%, compared with 18.4% for resection or anastomotic revision.

In a systematic review of 15 studies, de Vries et al found that postponing intestinal failure surgery in patients with enteric fistulas led to a lower rate of recurrence, though they were not able to define the optimal timing of such surgery.[29]